Structural basis for maintenance of bacterial outer membrane lipid asymmetry

Abellón-Ruiz, Javier and Kaptan, Shreyas S. and Baslé, Arnaud and Claudi, Beatrice and Bumann, Dirk and Kleinekathöfer, Ulrich and van den Berg, Bert. (2017) Structural basis for maintenance of bacterial outer membrane lipid asymmetry. Nature Microbiology, 2 (12). pp. 1616-1623.

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Official URL: http://edoc.unibas.ch/57180/

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The Gram-negative bacterial outer membrane (OM) is a unique bilayer that forms an efficient permeation barrier to protect the cell from noxious compounds (1)(,)(2) . The defining characteristic of the OM is lipid asymmetry, with phospholipids comprising the inner leaflet and lipopolysaccharides comprising the outer leaflet (1-3) . This asymmetry is maintained by the Mla pathway, a six-component system that is widespread in Gram-negative bacteria and is thought to mediate retrograde transport of misplaced phospholipids from the outer leaflet of the OM to the cytoplasmic membrane (4) . The OM lipoprotein MlaA performs the first step in this process via an unknown mechanism that does not require external energy input. Here we show, using X-ray crystallography, molecular dynamics simulations and in vitro and in vivo functional assays, that MlaA is a monomeric α-helical OM protein that functions as a phospholipid translocation channel, forming a ~20-Å-thick doughnut embedded in the inner leaflet of the OM with a central, amphipathic pore. This architecture prevents access of inner leaflet phospholipids to the pore, but allows outer leaflet phospholipids to bind to a pronounced ridge surrounding the channel, followed by diffusion towards the periplasmic space. Enterobacterial MlaA proteins form stable complexes with OmpF/C (5,6) , but the porins do not appear to play an active role in phospholipid transport. MlaA represents a lipid transport protein that selectively removes outer leaflet phospholipids to help maintain the essential barrier function of the bacterial OM.The crystal structure of MlaA, coupled with simulations of its interaction with phospholipids, elucidates how this outer membrane lipoprotein acts as a phospholipid translocation channel to maintain the asymmetric composition of the outer membrane.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Bumann)
UniBasel Contributors:Bumann, Dirk and Claudi, Beatrice
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:28 May 2018 07:41
Deposited On:28 May 2018 07:41

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